The focus of the previous three posts (Part One, Part Two, and Part Three) has been on reviewing various aspects of a paper recently published on the three-year milestone data of a clinical study in which study subjects had their own BMC injected into a 1-level or 2-level degenerative disc pathology in an attempt to mitigate low back pain. As indicated in each of the posts, I am a co-author on this paper, and the two previous papers in the series. I will complete my review of the relationship of the CD34+ cell composition of the patient’s BMC in terms of pain relief (VAS) and improved functionality (ODI) in this post. I also will address the potential that a placebo effect could account for the benefit demonstrated by the patients remaining in the study at the three-year milestone.
I left off referring to Figures 3c and 3d in the most recent publication. The bad news is that for patients with <1 million CD34+ cells per mL of injectate their average VAS result at the three-year milestone definitely has headed in a more painful direction. In contrast, those patients who received more than 2 million CD34+ cells per mL of injectate remained relatively flat in their average VAS values from the two-year milestone, while it would appear there was a slightly less painful trend for the 1-2 million CD34+ cells per mL of injectate sub-population. The ODI data showed a slight uptick at the three-year milestone for the <1 and >2 million CD34+ cells per mL of injectate sub-populations, but there was a slight reduction in pain for the in-betweeners. This probably reflects the influence of one or two of the patients in each group driving the trend, since the sub-populations are small.
Overall, the publication shows that 77% of the original enrolled discs (and the humans attached to those discs) remained in the study out to the endpoint of three years. There also were no serious complications associated with the procedure, in part because the patients did not require a general anesthetic, but received conscious sedation instead.
I would like to forestall neurosurgeons from trying to play the placebo effect card to account for the improvements in VAS and ODI demonstrated in the study, since this wasn’t a double-blind, placebo controlled clinical study. No way is this a placebo effect. First off, there were 20 patients who were active at the three-year milestone—a level of retention not reported in other intradiscal injection studies. There also is the data reported in the publication that shows the degree of improvement of VAS and ODI varied directly with threshold levels of CFU-Fs and CD34+ cells injected. Just to be clear, cell analysis is an objective clinical outcome, and objective clinical outcomes aren’t influenced by a placebo effect. So, it is hard for me to understand how the degree of pain relief or improved functionality could vary based on the level of MSCs and HSCs present in a patient’s BMC if the therapeutic benefit is just in a patient’s head.
Finally, although the link to a Mesoblast press release on their study of a donor-derived MSC injection to treat degenerative disc pathology (i.e., discogenic low back pain) no longer is active, I recall that in their double-blind, placebo controlled study they reported a 11-13% placebo effect out to two-years. If you apply that frequency to the Pettine study it means that three study subjects out of the 26 originally enrolled would feel better because of a placebo effect. Let’s assume that all three of the placebo effect patients made it to the three-year milestone, which would leave 65% of the study subjects with pain reduction as a result of the BMC injection. No way is the benefit due to a placebo effect.
The focus in my quartet of posts on the clinical study on BMC intra-discal treatment for degenerative disc pathology and low back pain reported in the three-year milestone publication has been on clinical outcomes and cell analysis data, since this combination of data rarely appears in the orthopedic clinical literature, except for papers with Dr. Philippe Hernigou as an author. But I would like to finish by pointing out that the paper also offers an intriguing comparison between the results for the study’s BMC treatment outcomes and publications covering clinical studies of more traditional surgical treatments (e.g., spinal fusion and total disc replacement) for degenerative disc pathology (i.e., discogenic low back pain) in terms of reducing pain and improving functionality after surgical intervention. I will close with a conclusion from the paper:
“The morbidity and cost of this percutaneous procedure are substantially less than a surgical option and the clinical results appear to be similar or superior to surgery for chronic discogenic low back pain.”